A Human CD4+ T Cell Epitope in the Influenza Hemagglutinin Is Cross-Reactive to Influenza A Virus Subtypes and to Influenza B Virus
Identifieur interne : 000003 ( PascalFrancis/Corpus ); précédent : 000002; suivant : 000004A Human CD4+ T Cell Epitope in the Influenza Hemagglutinin Is Cross-Reactive to Influenza A Virus Subtypes and to Influenza B Virus
Auteurs : Jenny Aurielle B. Babon ; John Cruz ; Francis A. Ennis ; LIUSONG YIN ; Masanori TerajimaSource :
- Journal of virology [ 0022-538X ] ; 2012.
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English descriptors
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Abstract
The hemagglutinin protein (HA) of the influenza virus family is a major antigen for protective immunity. Thus, it is a relevant target for developing vaccines. Here, we describe a human CD4+ T cell epitope in the influenza virus HA that lies in the fusion peptide of the HA. This epitope is well conserved in all 16 subtypes of the HA protein of influenza A virus and the HA protein of influenza B virus. By stimulating peripheral blood mononuclear cells (PBMCs) from a healthy adult donor with peptides covering the entire HA protein based on the sequence of A/Japan/305/1957 (H2N2), we generated a T cell line specific to this epitope. This CD4+ T cell line recognizes target cells infected with influenza A virus seasonal H1N1 and H3N2 strains, a reassortant H2N1 strain, the 2009 pandemic H1N1 strain, and influenza B virus in cytotoxicity assays and intracellular-cytokine-staining assays. It also lysed target cells infected with avian H5N1 virus. We screened healthy adult PBMCs for T cell responses specific to this epitope and found individuals who had ex vivo gamma interferon (IFN-γ) responses to the peptide epitope in enzyme-linked immunospot (ELISPOT) assays. Almost all donors who responded to the epitope had the HLA-DRB1*09 allele, a relatively common HLA allele. Although natural infection or standard vaccination may not induce strong T and B cell responses to this highly conserved epitope in the fusion peptide, it may be possible to develop a vaccination strategy to induce these CD4+ T cells, which are cross-reactive to both influenza A and B viruses.
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| NO : | PASCAL 12-0347785 INIST |
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| ET : | A Human CD4+ T Cell Epitope in the Influenza Hemagglutinin Is Cross-Reactive to Influenza A Virus Subtypes and to Influenza B Virus |
| AU : | BABON (Jenny Aurielle B.); CRUZ (John); ENNIS (Francis A.); LIUSONG YIN; TERAJIMA (Masanori) |
| AF : | Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School/Worcester, Massachusetts/Etats-Unis (1 aut., 2 aut., 3 aut., 5 aut.); Immunology and Virology, University of Massachusetts Medical School/Worcester, Massachusetts/Etats-Unis (1 aut., 3 aut., 4 aut., 5 aut.); Department of Pathology, University of Massachusetts Medical School/Worcester, Massachusetts/Etats-Unis (4 aut.) |
| DT : | Publication en série; Niveau analytique |
| SO : | Journal of virology; ISSN 0022-538X; Etats-Unis; Da. 2012; Vol. 86; No. 17; Pp. 9233-9243; Bibl. 85 ref. |
| LA : | Anglais |
| EA : | The hemagglutinin protein (HA) of the influenza virus family is a major antigen for protective immunity. Thus, it is a relevant target for developing vaccines. Here, we describe a human CD4+ T cell epitope in the influenza virus HA that lies in the fusion peptide of the HA. This epitope is well conserved in all 16 subtypes of the HA protein of influenza A virus and the HA protein of influenza B virus. By stimulating peripheral blood mononuclear cells (PBMCs) from a healthy adult donor with peptides covering the entire HA protein based on the sequence of A/Japan/305/1957 (H2N2), we generated a T cell line specific to this epitope. This CD4+ T cell line recognizes target cells infected with influenza A virus seasonal H1N1 and H3N2 strains, a reassortant H2N1 strain, the 2009 pandemic H1N1 strain, and influenza B virus in cytotoxicity assays and intracellular-cytokine-staining assays. It also lysed target cells infected with avian H5N1 virus. We screened healthy adult PBMCs for T cell responses specific to this epitope and found individuals who had ex vivo gamma interferon (IFN-γ) responses to the peptide epitope in enzyme-linked immunospot (ELISPOT) assays. Almost all donors who responded to the epitope had the HLA-DRB1*09 allele, a relatively common HLA allele. Although natural infection or standard vaccination may not induce strong T and B cell responses to this highly conserved epitope in the fusion peptide, it may be possible to develop a vaccination strategy to induce these CD4+ T cells, which are cross-reactive to both influenza A and B viruses. |
| CC : | 002A05C10 |
| FD : | Homme; Virus grippal A; Virus grippal B; Lymphocyte T CD4; Déterminant antigénique; Hémagglutinine; Soustype; Grippe |
| FG : | Influenzavirus A; Orthomyxoviridae; Virus; Influenzavirus B; Virose; Infection |
| ED : | Human; Influenza A virus; Influenza B virus; CD4 T lymphocyte; Antigenic determinant; Hemagglutinin; Subtype; Influenza |
| EG : | Influenzavirus A; Orthomyxoviridae; Virus; Influenzavirus B; Viral disease; Infection |
| SD : | Hombre; Influenza A virus; Influenza B virus; Linfocito T CD4; Determinante antigénico; Hemoaglutinina; Subtipo; Gripe |
| LO : | INIST-13592.354000504078900280 |
| ID : | 12-0347785 |
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Babon</name><affiliation><inist:fA14 i1="01"><s1>Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School</s1><s2>Worcester, Massachusetts</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ></inist:fA14></affiliation><affiliation><inist:fA14 i1="02"><s1>Immunology and Virology, University of Massachusetts Medical School</s1><s2>Worcester, Massachusetts</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Cruz, John" sort="Cruz, John" uniqKey="Cruz J" first="John" last="Cruz">John Cruz</name><affiliation><inist:fA14 i1="01"><s1>Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School</s1><s2>Worcester, Massachusetts</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Ennis, Francis A" sort="Ennis, Francis A" uniqKey="Ennis F" first="Francis A." last="Ennis">Francis A. Ennis</name><affiliation><inist:fA14 i1="01"><s1>Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School</s1><s2>Worcester, Massachusetts</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ></inist:fA14></affiliation><affiliation><inist:fA14 i1="02"><s1>Immunology and Virology, University of Massachusetts Medical School</s1><s2>Worcester, Massachusetts</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Liusong Yin" sort="Liusong Yin" uniqKey="Liusong Yin" last="Liusong Yin">LIUSONG YIN</name><affiliation><inist:fA14 i1="02"><s1>Immunology and Virology, University of Massachusetts Medical School</s1><s2>Worcester, Massachusetts</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ></inist:fA14></affiliation><affiliation><inist:fA14 i1="03"><s1>Department of Pathology, University of Massachusetts Medical School</s1><s2>Worcester, Massachusetts</s2><s3>USA</s3><sZ>4 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Terajima, Masanori" sort="Terajima, Masanori" uniqKey="Terajima M" first="Masanori" last="Terajima">Masanori Terajima</name><affiliation><inist:fA14 i1="01"><s1>Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School</s1><s2>Worcester, Massachusetts</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ></inist:fA14></affiliation><affiliation><inist:fA14 i1="02"><s1>Immunology and Virology, University of Massachusetts Medical School</s1><s2>Worcester, Massachusetts</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ></inist:fA14></affiliation></author></analytic><series><title level="j" type="main">Journal of virology</title><title level="j" type="abbreviated">J. virol.</title><idno type="ISSN">0022-538X</idno><imprint><date when="2012">2012</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Journal of virology</title><title level="j" type="abbreviated">J. virol.</title><idno type="ISSN">0022-538X</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Antigenic determinant</term><term>CD4 T lymphocyte</term><term>Hemagglutinin</term><term>Human</term><term>Influenza</term><term>Influenza A virus</term><term>Influenza B virus</term><term>Subtype</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Homme</term><term>Virus grippal A</term><term>Virus grippal B</term><term>Lymphocyte T CD4</term><term>Déterminant antigénique</term><term>Hémagglutinine</term><term>Soustype</term><term>Grippe</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The hemagglutinin protein (HA) of the influenza virus family is a major antigen for protective immunity. Thus, it is a relevant target for developing vaccines. Here, we describe a human CD4<sup>+</sup> T cell epitope in the influenza virus HA that lies in the fusion peptide of the HA. This epitope is well conserved in all 16 subtypes of the HA protein of influenza A virus and the HA protein of influenza B virus. By stimulating peripheral blood mononuclear cells (PBMCs) from a healthy adult donor with peptides covering the entire HA protein based on the sequence of A/Japan/305/1957 (H2N2), we generated a T cell line specific to this epitope. This CD4<sup>+</sup> T cell line recognizes target cells infected with influenza A virus seasonal H1N1 and H3N2 strains, a reassortant H2N1 strain, the 2009 pandemic H1N1 strain, and influenza B virus in cytotoxicity assays and intracellular-cytokine-staining assays. It also lysed target cells infected with avian H5N1 virus. We screened healthy adult PBMCs for T cell responses specific to this epitope and found individuals who had ex vivo gamma interferon (IFN-γ) responses to the peptide epitope in enzyme-linked immunospot (ELISPOT) assays. Almost all donors who responded to the epitope had the HLA-DRB1<sup>*</sup>09 allele, a relatively common HLA allele. Although natural infection or standard vaccination may not induce strong T and B cell responses to this highly conserved epitope in the fusion peptide, it may be possible to develop a vaccination strategy to induce these CD4<sup>+</sup> T cells, which are cross-reactive to both influenza A and B viruses.</div></front></TEI><inist><standard h6="B"><pA><fA01 i1="01" i2="1"><s0>0022-538X</s0></fA01><fA03 i2="1"><s0>J. virol.</s0></fA03><fA05><s2>86</s2></fA05><fA06><s2>17</s2></fA06><fA08 i1="01" i2="1" l="ENG"><s1>A Human CD4<sup>+</sup> T Cell Epitope in the Influenza Hemagglutinin Is Cross-Reactive to Influenza A Virus Subtypes and to Influenza B Virus</s1></fA08><fA11 i1="01" i2="1"><s1>BABON (Jenny Aurielle B.)</s1></fA11><fA11 i1="02" i2="1"><s1>CRUZ (John)</s1></fA11><fA11 i1="03" i2="1"><s1>ENNIS (Francis A.)</s1></fA11><fA11 i1="04" i2="1"><s1>LIUSONG YIN</s1></fA11><fA11 i1="05" i2="1"><s1>TERAJIMA (Masanori)</s1></fA11><fA14 i1="01"><s1>Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School</s1><s2>Worcester, Massachusetts</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ></fA14><fA14 i1="02"><s1>Immunology and Virology, University of Massachusetts Medical School</s1><s2>Worcester, Massachusetts</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ></fA14><fA14 i1="03"><s1>Department of Pathology, University of Massachusetts Medical School</s1><s2>Worcester, Massachusetts</s2><s3>USA</s3><sZ>4 aut.</sZ></fA14><fA20><s1>9233-9243</s1></fA20><fA21><s1>2012</s1></fA21><fA23 i1="01"><s0>ENG</s0></fA23><fA43 i1="01"><s1>INIST</s1><s2>13592</s2><s5>354000504078900280</s5></fA43><fA44><s0>0000</s0><s1>© 2012 INIST-CNRS. All rights reserved.</s1></fA44><fA45><s0>85 ref.</s0></fA45><fA47 i1="01" i2="1"><s0>12-0347785</s0></fA47><fA60><s1>P</s1></fA60><fA61><s0>A</s0></fA61><fA64 i1="01" i2="1"><s0>Journal of virology</s0></fA64><fA66 i1="01"><s0>USA</s0></fA66><fC01 i1="01" l="ENG"><s0>The hemagglutinin protein (HA) of the influenza virus family is a major antigen for protective immunity. Thus, it is a relevant target for developing vaccines. Here, we describe a human CD4<sup>+</sup> T cell epitope in the influenza virus HA that lies in the fusion peptide of the HA. This epitope is well conserved in all 16 subtypes of the HA protein of influenza A virus and the HA protein of influenza B virus. By stimulating peripheral blood mononuclear cells (PBMCs) from a healthy adult donor with peptides covering the entire HA protein based on the sequence of A/Japan/305/1957 (H2N2), we generated a T cell line specific to this epitope. This CD4<sup>+</sup> T cell line recognizes target cells infected with influenza A virus seasonal H1N1 and H3N2 strains, a reassortant H2N1 strain, the 2009 pandemic H1N1 strain, and influenza B virus in cytotoxicity assays and intracellular-cytokine-staining assays. It also lysed target cells infected with avian H5N1 virus. We screened healthy adult PBMCs for T cell responses specific to this epitope and found individuals who had ex vivo gamma interferon (IFN-γ) responses to the peptide epitope in enzyme-linked immunospot (ELISPOT) assays. Almost all donors who responded to the epitope had the HLA-DRB1<sup>*</sup>09 allele, a relatively common HLA allele. Although natural infection or standard vaccination may not induce strong T and B cell responses to this highly conserved epitope in the fusion peptide, it may be possible to develop a vaccination strategy to induce these CD4<sup>+</sup> T cells, which are cross-reactive to both influenza A and B viruses.</s0></fC01><fC02 i1="01" i2="X"><s0>002A05C10</s0></fC02><fC03 i1="01" i2="X" l="FRE"><s0>Homme</s0><s5>01</s5></fC03><fC03 i1="01" i2="X" l="ENG"><s0>Human</s0><s5>01</s5></fC03><fC03 i1="01" i2="X" l="SPA"><s0>Hombre</s0><s5>01</s5></fC03><fC03 i1="02" i2="X" l="FRE"><s0>Virus grippal A</s0><s2>NW</s2><s5>02</s5></fC03><fC03 i1="02" i2="X" l="ENG"><s0>Influenza A virus</s0><s2>NW</s2><s5>02</s5></fC03><fC03 i1="02" i2="X" l="SPA"><s0>Influenza A virus</s0><s2>NW</s2><s5>02</s5></fC03><fC03 i1="03" i2="X" l="FRE"><s0>Virus grippal B</s0><s2>NW</s2><s5>03</s5></fC03><fC03 i1="03" i2="X" l="ENG"><s0>Influenza B virus</s0><s2>NW</s2><s5>03</s5></fC03><fC03 i1="03" i2="X" l="SPA"><s0>Influenza B virus</s0><s2>NW</s2><s5>03</s5></fC03><fC03 i1="04" i2="X" l="FRE"><s0>Lymphocyte T CD4</s0><s5>05</s5></fC03><fC03 i1="04" i2="X" l="ENG"><s0>CD4 T lymphocyte</s0><s5>05</s5></fC03><fC03 i1="04" i2="X" l="SPA"><s0>Linfocito T CD4</s0><s5>05</s5></fC03><fC03 i1="05" i2="X" l="FRE"><s0>Déterminant antigénique</s0><s5>06</s5></fC03><fC03 i1="05" i2="X" l="ENG"><s0>Antigenic determinant</s0><s5>06</s5></fC03><fC03 i1="05" i2="X" l="SPA"><s0>Determinante antigénico</s0><s5>06</s5></fC03><fC03 i1="06" i2="X" l="FRE"><s0>Hémagglutinine</s0><s5>07</s5></fC03><fC03 i1="06" i2="X" l="ENG"><s0>Hemagglutinin</s0><s5>07</s5></fC03><fC03 i1="06" i2="X" l="SPA"><s0>Hemoaglutinina</s0><s5>07</s5></fC03><fC03 i1="07" i2="X" l="FRE"><s0>Soustype</s0><s5>08</s5></fC03><fC03 i1="07" i2="X" l="ENG"><s0>Subtype</s0><s5>08</s5></fC03><fC03 i1="07" i2="X" l="SPA"><s0>Subtipo</s0><s5>08</s5></fC03><fC03 i1="08" i2="X" l="FRE"><s0>Grippe</s0><s5>14</s5></fC03><fC03 i1="08" i2="X" l="ENG"><s0>Influenza</s0><s5>14</s5></fC03><fC03 i1="08" i2="X" l="SPA"><s0>Gripe</s0><s5>14</s5></fC03><fC07 i1="01" i2="X" l="FRE"><s0>Influenzavirus A</s0><s2>NW</s2></fC07><fC07 i1="01" i2="X" l="ENG"><s0>Influenzavirus A</s0><s2>NW</s2></fC07><fC07 i1="01" i2="X" l="SPA"><s0>Influenzavirus A</s0><s2>NW</s2></fC07><fC07 i1="02" i2="X" l="FRE"><s0>Orthomyxoviridae</s0><s2>NW</s2></fC07><fC07 i1="02" i2="X" l="ENG"><s0>Orthomyxoviridae</s0><s2>NW</s2></fC07><fC07 i1="02" i2="X" l="SPA"><s0>Orthomyxoviridae</s0><s2>NW</s2></fC07><fC07 i1="03" i2="X" l="FRE"><s0>Virus</s0><s2>NW</s2></fC07><fC07 i1="03" i2="X" l="ENG"><s0>Virus</s0><s2>NW</s2></fC07><fC07 i1="03" i2="X" l="SPA"><s0>Virus</s0><s2>NW</s2></fC07><fC07 i1="04" i2="X" l="FRE"><s0>Influenzavirus B</s0><s2>NW</s2></fC07><fC07 i1="04" i2="X" l="ENG"><s0>Influenzavirus B</s0><s2>NW</s2></fC07><fC07 i1="04" i2="X" l="SPA"><s0>Influenzavirus B</s0><s2>NW</s2></fC07><fC07 i1="05" i2="X" l="FRE"><s0>Virose</s0></fC07><fC07 i1="05" i2="X" l="ENG"><s0>Viral disease</s0></fC07><fC07 i1="05" i2="X" l="SPA"><s0>Virosis</s0></fC07><fC07 i1="06" i2="X" l="FRE"><s0>Infection</s0></fC07><fC07 i1="06" i2="X" l="ENG"><s0>Infection</s0></fC07><fC07 i1="06" i2="X" l="SPA"><s0>Infección</s0></fC07><fN21><s1>268</s1></fN21><fN44 i1="01"><s1>OTO</s1></fN44><fN82><s1>OTO</s1></fN82></pA></standard><server><NO>PASCAL 12-0347785 INIST</NO><ET>A Human CD4<sup>+</sup> T Cell Epitope in the Influenza Hemagglutinin Is Cross-Reactive to Influenza A Virus Subtypes and to Influenza B Virus</ET><AU>BABON (Jenny Aurielle B.); CRUZ (John); ENNIS (Francis A.); LIUSONG YIN; TERAJIMA (Masanori)</AU><AF>Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School/Worcester, Massachusetts/Etats-Unis (1 aut., 2 aut., 3 aut., 5 aut.); Immunology and Virology, University of Massachusetts Medical School/Worcester, Massachusetts/Etats-Unis (1 aut., 3 aut., 4 aut., 5 aut.); Department of Pathology, University of Massachusetts Medical School/Worcester, Massachusetts/Etats-Unis (4 aut.)</AF><DT>Publication en série; Niveau analytique</DT><SO>Journal of virology; ISSN 0022-538X; Etats-Unis; Da. 2012; Vol. 86; No. 17; Pp. 9233-9243; Bibl. 85 ref.</SO><LA>Anglais</LA><EA>The hemagglutinin protein (HA) of the influenza virus family is a major antigen for protective immunity. Thus, it is a relevant target for developing vaccines. Here, we describe a human CD4<sup>+</sup> T cell epitope in the influenza virus HA that lies in the fusion peptide of the HA. This epitope is well conserved in all 16 subtypes of the HA protein of influenza A virus and the HA protein of influenza B virus. By stimulating peripheral blood mononuclear cells (PBMCs) from a healthy adult donor with peptides covering the entire HA protein based on the sequence of A/Japan/305/1957 (H2N2), we generated a T cell line specific to this epitope. This CD4<sup>+</sup> T cell line recognizes target cells infected with influenza A virus seasonal H1N1 and H3N2 strains, a reassortant H2N1 strain, the 2009 pandemic H1N1 strain, and influenza B virus in cytotoxicity assays and intracellular-cytokine-staining assays. It also lysed target cells infected with avian H5N1 virus. We screened healthy adult PBMCs for T cell responses specific to this epitope and found individuals who had ex vivo gamma interferon (IFN-γ) responses to the peptide epitope in enzyme-linked immunospot (ELISPOT) assays. Almost all donors who responded to the epitope had the HLA-DRB1<sup>*</sup>09 allele, a relatively common HLA allele. Although natural infection or standard vaccination may not induce strong T and B cell responses to this highly conserved epitope in the fusion peptide, it may be possible to develop a vaccination strategy to induce these CD4<sup>+</sup> T cells, which are cross-reactive to both influenza A and B viruses.</EA><CC>002A05C10</CC><FD>Homme; Virus grippal A; Virus grippal B; Lymphocyte T CD4; Déterminant antigénique; Hémagglutinine; Soustype; Grippe</FD><FG>Influenzavirus A; Orthomyxoviridae; Virus; Influenzavirus B; Virose; Infection</FG><ED>Human; Influenza A virus; Influenza B virus; CD4 T lymphocyte; Antigenic determinant; Hemagglutinin; Subtype; Influenza</ED><EG>Influenzavirus A; Orthomyxoviridae; Virus; Influenzavirus B; Viral disease; Infection</EG><SD>Hombre; Influenza A virus; Influenza B virus; Linfocito T CD4; Determinante antigénico; Hemoaglutinina; Subtipo; Gripe</SD><LO>INIST-13592.354000504078900280</LO><ID>12-0347785</ID></server></inist></record>Pour manipuler ce document sous Unix (Dilib)
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